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However, combined antiretroviral therapy (cART) aids in viral latency and prevents the progression of HIV-1 infection into acquired immunodeficiency syndrome (AIDS). cART has extended many lives, but people living with HIV-1 (PLWH) face lifelong ailments such as HIV-associated neurocognitive disorders (HAND) that range from asymptomatic HAND to HIV-1-associated dementia. HAND has been attributed to chronic inflammation and low-level infection within the central nervous system (CNS) caused by proinflammatory cytokines and viral products. These molecules are shuttled into the CNS within extracellular vesicles (EVs), lipid bound nanoparticles, and are released from cells as a form of intercellular communication. This study investigates the impact of cannabidiol (CBD), as a promising and potential therapeutic for HAND patients, and a similar synthetic molecule, HU308, on the EVs released from HIV-1-infected myeloid cells as well as HIV-1-infected 3D neurospheres. The data shows that both CBD and HU308 decrease non-coding and coding viral RNA (TAR and env) as well as proinflammatory cytokines as IL-1\u03b2 and TNF-\u03b1 mRNA. This decrease in viral RNA occurs in in vitro differentiated primary macrophages, in EVs released from HIV-1-infected cells monocytes, and infected neurospheres. Furthermore, a 3D neurosphere model shows an overall decrease in proinflammatory mRNA with HU308. Finally, using a humanized mouse model of HIV-1 infection, plasma viral RNA was shown to significantly decrease with HU308 alone and was most effective in combination with cART, even when compared to the typical cART treatment. Overall, CBD or HU308 may be a viable option to decrease EV release and associated cytokines which would dampen the virus spread and may be used in effective treatment of HAND in combination with cART.<\/jats:p>","DOI":"10.3390\/ph16081147","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T10:13:57Z","timestamp":1692008037000},"page":"1147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Use of CBD and Its Synthetic Analog HU308 in HIV-1-Infected Myeloid Cells"],"prefix":"10.3390","volume":"16","author":[{"given":"Anastasia","family":"Williams","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3842-5146","authenticated-orcid":false,"given":"Pooja","family":"Khatkar","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather","family":"Branscome","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8658-6863","authenticated-orcid":false,"given":"Yuriy","family":"Kim","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Erickson","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4321-9777","authenticated-orcid":false,"given":"Mohammad-Ali","family":"Jenabian","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences and CERMO-FC Research Center, University of Quebec in Montreal, Montreal, QC H2L 2C4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4547-714X","authenticated-orcid":false,"given":"Cecilia T.","family":"Costiniuk","sequence":"additional","affiliation":[{"name":"Infectious Diseases and Immunity in Global Health Program, Research Institute of the McGill University Health Centre, Montreal, QC H4A 3J1, Canada"},{"name":"Department of Medicine, Division of Infectious Diseases and Chronic Viral Illness Service, McGill University Health Centre, Montreal, QC H4A 3J1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9681-2780","authenticated-orcid":false,"given":"Fatah","family":"Kashanchi","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Virology, School of Systems Biology, George Mason University, Discovery Hall Room 182, 10900 University Blvd., Manassas, VA 20110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,12]]},"reference":[{"key":"ref_1","unstructured":"(2023, June 29). 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